1. Field
One or more exemplary embodiments relate to an apparatus for fabricating a biochip by using a photolithographic method without using a mask, and for optically detecting the biochip so as to read the biochip.
2. Description of the Related Art
A biochip is a biometric device made by combining biogenic organic materials such as enzymes, peptides, proteins, antibodies, and deoxyribonucleic acids (“DNAs”) of living creatures, microorganisms, and cells, organs, and nerves of animals and plants into a microchip similar to a semiconductor chip. In particular, a DNA chip is a device for detecting DNAs. The DNA chip is made by arranging several hundred DNAs to ten million DNAs having different base sequences, of which functions in a cell are clarified, within a small space on a substrate. Furthermore, the DNAs are arranged in a single spiral shape instead of a double spiral shape on the substrate. The substrate can be a glass substrate or a semiconductor substrate for example. A collection of single spiral shaped DNAs having the same base sequence is generally referred to as a spot and nearly twenty to hundred bases are connected to form a single spot.
When genetic material of a sample is dropped onto such a DNA chip, only genes corresponding to a specific spot, i.e., genes having a complementary sequence to a base sequence of the specific spot, are combined with the corresponding spot. Furthermore, genes that are not combined with spots in the DNA chip are washed away. Functions of base sequences of spots arranged on a DNA chip are already known, and thus genetic information of the sample can be easily obtained by identifying spots combined with genes on the DNA chip. Accordingly, aspects of unique genetic expressions or mutations in a specific cell or a tissue can be analyzed relatively fast by using the DNA chip. Furthermore, the DNA chip can also be used in massive analysis of genetic expressions, single nucleotide polymorphism and copy number variation in a gene, a pathogenic bacteria infection test, an antibiotic-resistance test, research on biological reactions with respect to environmental factors, food safety inspection, identification of criminals, development of new drugs, and medical inspection of animals and plants.
Such a biochip can be fabricated by stacking DNA bases such as adenine (A), guanine (G), cytosine (C), and thymine (T) in different sequences on spots of the biochip, for example, twenty to hundred times. A very precise fabricating method is utilized to form several ten million of different spots in a single biochip with exact base sequences. A representative method of fabricating a biochip is a photolithographic method which is the same method used for fabricating a semiconductor. In the photolithographic method, a biochip except for an area for reacting with a specific base is covered by a mask and light is projected onto the biochip. In this exemplary embodiment, all bases used for reaction are combined with a photolabile material such that the bases cannot combine with each other. However, when light is projected, the photolabile material is decomposed from the bases and thus a base onto which light is projected can combine with another base. Accordingly, the specific base can be combined with bases that are not covered by the mask and are exposed to light. In the photolithographic method, although the biochip can be precisely fabricated, a fabricating time is relatively long and a fabricating cost is relatively high because the lithography equipment is relatively expensive and a large number of masks corresponding to about four times of the number of stacked bases are used.
Meanwhile, when a sample is analyzed, various methods for identifying spots in a DNA chip, which are combined with genes of the sample, have been suggested. A fluorescent light detection method is a representative example of the suggested methods. In the fluorescent light detection method, a base including a fluorescent material for emitting light of a specific color when excited by excitation light is combined with genetic material of the sample. The genetic material of the sample is dropped onto a DNA chip and then a fluorescent image obtained by projecting excitation light onto the DNA chip is analyzed, thereby indentifying spots combined with genes of the sample.
In general, a photodetector for obtaining a fluorescent image by projecting excitation light onto a DNA chip obtains a fluorescent image by detecting a DNA chip in pixels of approximately 0.1 μm to 10 μm. Such a basic detecting unit is referred as a segment, and a single spot is formed of several segments to several tens of segments (e.g., 32 segments). A segment is a basic scanning unit in a spot detection method and a panel formed of several hundred spot arrays to several thousand spot arrays (e.g., 5,000 spot arrays) is a basic scanning unit in an image detection method. Generally, the spot detection method uses a photomultiplier tube (“PMT”) as the photodetector and the image detection method uses a charge-coupled device (“CCD”), a complementary metal-oxide-semiconductor (“CMOS”) image sensor (“CIS”), or the like as the photodetector. A bio-chip scanner, i.e., a fluorescence detector, may read a DNA chip by scanning each segment or panel in the DNA chip.
However, since a process of fabricating a DNA chip is separated from a process of analyzing a sample, and an apparatus for fabricating the DNA chip is separated from a fluorescence detector for reading the DNA chip, exposure to an external environment is unavoidable when the DNA chip is reprocessed, stored, and used to analyze a sample, which degrades a reliability of the DNA chip.